The broad aim of the project proposed herein is to elucidate the mechanisms by which the postnatal development of the rat intestine is regulated. It is known that dramatic changes of intestinal morphology and enzymology occur during the third postnatal week. The timing of these changes coincides wih the natural period of weaning in this species and the nature of the changes is such as to facilitate this dietary transition. The developmental patterns of the disaccharidases illustrates this point: during the third week of life lactase activity is found to decline whereas sucrase and maltase increase markedly. Earlier work, including my own, has suggested that the glucocorticoid hormones have a causal role in virtually all of the changes that occur at this time and that intestinal tissue becomes increasingly sensitive to glucocorticoid through the second postnatal week until a threshold is reached at the beginning of the third week. It is my aim to determine the molecular basis of this increasing sensitivity, i.e. to find factors which either negate glucocorticoid sensitivity in very young animals or which facilitate glucocorticoid action during the second and third weeks. Such factors could be either intrinsic to the intestine itself (e.g., intracellular steps involved in the action of glucocorticoids) or of extrinsic origin (e.g., another hormone or the dietary change). Thus the approach to the question will be threefold: 1) To study the various steps in glucocorticoid action and determine whether any of these has a developmental pattern that would explain the known pattern of responsiveness of the intestine. 2) To determine whether thyroxine, whose circulating concentration rises at the end of the second postnatal week, facilitates glucocoticoid action on the intestine. 3) To determine whether the dietary change of weaning has any modulating effect on the enzymic changes that usually occur in the intestine during the third week.